Monitor G-CSF Study Treatment patterns and outcomes in the prophylaxis of chemotherapy induced neutropenia with biosimilar filgrastim (Zarzio )

Transcription

1 Monitor G-CSF Study Treatment patterns and outcomes in the prophylaxis of chemotherapy induced neutropenia with biosimilar filgrastim (Zarzio ) Heinz Ludwig Wilhelminen Cancer Research Institute c/o I Medizinische Abteilung, Zentrum für Onkologe und Hämatologie Wilhelminenspital, Vienna, Austria Pere Gascón, Matti Aapro, Carsten Bokemeyer, Mario Boccadoro, Matthew Turner, Kris Denhaerynck, Karen MacDonald, Ivo Abraham

2 Monitor G-CSF: A large prospective survey Goals Assess real-world treatment patterns, outcomes, and associated determinants of Zarzio prophylaxis for chemotherapy-induced FN Assess congruence of clinical practice with recommended guidelines Patients With solid tumors and hematologic malignancies receiving myelosuppressive chemotherapy Methods Observational study with follow up for up to 6 months Participants patients, 140 centers in 12 countries

3 No. of patients Patients 1496 patients were enrolled; evaluable sample n= % female (61.2%) ; median age 62 years; median BMI 25.7kg/m % had solid tumor, mainly breast (32.2%) or lung (23.8%) cancer Breast Lung Ovarian Prostate Bladder Lymphoma Multiple myeloma

4 low (<10%) medium (10-20%) high (>20%) Risk of FN Chemotherapy-related risk for FN

5 low (<10%) medium (10-20%) high (>20%) Risk of FN Chemotherapy-related risk for FN Patient-Related Risks per EORTC no concomitant antibiotic female Hb <12 g/dl age >65 history of prior FN renal, CV or liver disease advanced disease poor performance/nutrition All patients Patients with chemo risk 10-20%

6 Study population: Previous CIN & FN History Number % All patients CIN grade 4 episode 106 7,3% FN episode 27 1,9% CIN/FN-related hospitalization 33 2,3% CIN/FN-related chemotherapy disturbance 48 3,3% G-CSF therapy 55 3,8%

7 Study population: Previous CIN & FN History Number % All patients % Prior chemo CIN grade 4 episode 106 7,3% 23,0% FN episode 27 1,9% 5,9% CIN/FN-related hospitalization 33 2,3% 7,2% CIN/FN-related chemotherapy disturbance 48 3,3% 10,4% G-CSF therapy 55 3,8% 12,0%

8 Type and dose of G-CSF prophylaxis Primary Prophylaxis 1046 (72.3%) Secondary Prophylaxis 401 (27.7%) 30 MIU/day Dose patients at initiation cycles across study 815 (56,8%) 3182 (53,2%) 40 MIU/day 610 (42,5%) 2756 (46,0%)

9 Day of initiation of G-CSF pophylaxis by tumor category All Solid tumors Hematological malignancies 0 13,4% 16,0% 4,2% 1 30,7% 33,6% 20,4% 2 13,4% 14,9% 8,0% 3 9,1% 9,8% 6,9% 4 4,6% 4,1% 6,2% 5 6,8% 6,7% 7,2% 6 6,7% 3,4% 18,6% 7 7,2% 5,8% 12,2% 8 3,9% 2,5% 8,7% 9 1,0% 1,0% 0,9% 10 0,8% 0,6% 1,5% 11 0,6% 0,5% 1,1% 12 1,8% 1,1% 4,1% All patients 3,08% (Mean) 2,98% (Mean) P<0.001

10 Day (mean) of initiation of G-CSF prophylaxis by various parameters Day of initiation of prophylaxis All patients Mean SD 3,08 2,98 By type of prophylaxis p primary 3,19 3,00 secondary 2,63 2,87 < By chemotoxicity <10% 2,31 2, % 2,95 3,00 < % 3,34 2,96 By tumor type oncology 2,60 2,70 hematology 4,76 3,30 <0.001

11 What is the optimal time to start G-CSF? Kinetics of mean ANC levels after ACE TX in cycle 1 and in cycles 2-6 depending on time after start of chemotherapy Crawford J et al., Ann Oncol 1997

12 Duration of G-CSF prophylaxis Patients at initiation Cycles across study Duration in days Number Percentage Number Percentage 1-3 days ,0% ,5% 4-5 days ,0% ,9% 6 or more days ,0% ,6% patients at initiation cycles across study Concomitant antibiotic administered ,1% 609 8,0%

13 Gold standard: EORTC and ASCO guidelines STEP 1: Assess FN risk for the planned chemotherapy regimen The patient s FN risk should be routinely assessed prior to each chemotherapy cycle Dose-dense chemotherapy regimens should always be considered high risk for FN (FN risk 20%) 1 Patients with NHL > 65 years receiving curative chemotherapy should be considered at high risk of FN 2 FN risk 20% FN risk 10 20% FN risk <10% PROPHYLACTIC G-CSF RECOMMENDED STEP 2: Assess factors that may increase the risk of FN Age 65 years 1,2 No antibiotic prophylaxis 1 Advanced disease 1,2 Previous episode of FN 1,2 Serious co-morbidities 2 Poor performance status 1,2 Open wounds or active infections 2 Poor nutritional status 1,2 Female gender 1 Combined chemoradiotherapy 2 Cytopenias due to tumour bone marrow involvement 2 Haemoglobin <12 g/dl 1 G-CSF USE NOT INDICATED Overall FN risk 20% Overall FN risk <20% This algorithm represents a combined interpretation of the 2006 G-CSF guidelines of EORTC and ASCO Underlined factors have level I/II evidence according to EORTC 1. Aapro MS et al. Eur J Cancer 2006;42: NHL, non-hodgkin s lymphoma 2. Smith TJ, et al. J Clin Oncol. 2006;24:

14 Results: Congruence of prophylaxis with EORTC guidelines Under-prophylacted ,0% Correctly-prophylacted ,3% Over-prophylacted ,7%

15 % Clinical outcomes: incidence rates 25 Patients Cycles 22, ,2 10 9,5 5 3,9 5,9 6,1 1,4 1,5 2,8 6,7 0 CIN grade IV FN CIN/FN-related hospitalization CT disturbances COI COI = composite outcomes index: any occurrence of CIN grade IV, FN, CIN/FN-related hospitalizations, and/or CIN/FN-related chemotherapy disturbances

16 Neutropenia episodes by day of initiation of prophylaxis By day of initiation of prophylaxis All cycles (n, %) Day of chemo hours >72 hours p CIN grades 1 through ,3% 13,0% 13,4% 20,0% <0.001 CIN grades 3 or ,0% 6,7% 6,3% 13,4% <0.001 CIN grade ,9% 3,1% 2,8% 7,3% <0.001 FN 105 1,4% 1,0% 1,2% 2,1% 0,029 CIN/FN-related Hospitalizations 111 1,5% 1,9% 1,1% 1,8% n.s.

17 Neutropenia episodes by duration of G-CSF prophylaxis By duration of prophylaxis 1-3 days 4-5 days 6 days p CIN grades 1-4 CIN grade 3 & 4 CIN grade 4 FN CN/FN related hospitalisations 15,7% 13,4% 20,0% < ,1% 7,6% 10,3% 0,008 3,6% 3,9% 5,5% 0,015 1,2% 1,2% 2,2% 0,015 1,2% 1,4% 1,8% n.s.

18 CIN/FN-related chemotherapy distrbancies by duration of G- CSF prophylaxis By duration of prophylaxis All cycles 1-3 days 4-5 days 6 days p Any chemotherapy disturbance 174 2,0% 2,1% 4,7% <0.001 Chemotherapy dose reduction 46 0,6% 0,8% 1,0% n.s. Chemotherapy delay 142 2,0% 1,5% 3,9% <0.001 Chemotherapy cancellation 3 0,0% 0,1% 0,0% n.s. CIN/FN-related composite outcome ,0% 5,8% 9.3% < Includes any occurrence of CIN grade 4, FN, CIN/FN-related hospitalization, and/or CIN/FIN-related chemotherapy disturbance.

19 Neutropenia episodes by chemotoxicity All patients (n, %) <10% 10-20% >20% p CIN grades 1 through ,8% 29,9% 36,0% 34,8% n.s. CIN grades 3 or ,9% 14,9% 22,9% 25,0% 0,029 CIN grade ,2% 7,8% 11,9% 15,9% 0,010 FN 86 5,9% 3,9% 3,5% 8,9% <0.001 CIN/FN-related hospitalizations 88 6,1% 3,9% 5,4% 7,3% n.s.

20 CIN/FN related chemotherapy disturbancies by chemotoxicity All patients (n, %) <10% 10-20% >20% p Any chemotherapy disturbance 138 9,5% 8,4% 10,8% 8,6% n.s. Chemotherapy dose reduction 45 3,1% 3,9% 3,2% 2,8% n.s. Chemotherapy delay 113 7,8% 7,1% 8,9% 6,9% n.s. Chemotherapy cancellation 3 0,2% 0,0% 0,0% 0,5% n.s. CIN/FN-related composite outcome ,3% 16,9% 20,9% 25,2% 0,043 1 Includes any occurrence of CIN grade 4, FN, CIN/FN-related hospitalization, and/or CIN/FIN-related chemotherapy disturbance.

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24 Summary Primary G-CSF in real world clinical practice 72.3% of patients received primary G-CSF prophylaxis Correct in 55.3% Over-prophylacted in 27.7% Under-prophylacted in 17.0% Initiation of primary G-CSF prophylaxis was correct in 53.2% too early in 13.4% too late in 33.4% CIN (grade 4) episodes: 13.2% FN episodes: 5.9% CIN/FN related hospitalisations 6.1% CIN/FN related chemotherapy disturbancies:9.5%

25 Summary Primary G-CSF in real world clinical practice Delayed initiation of primary G-CSF prophylaxis (<72 hrs) increases risk for CIN and FN Secondary prophylaxis is associated with higher risk for CIN and FN and chemotherapy delay or other disturbances These data comfirm the importance of congruence with EORTC guidelines, paricularly regarding initiation of therapy wihin 72 hours